Diisopropylethylamine → tert-butyl (1S)-1-{[[(1S,2E)-3-cyano-1-isopropyl-2-propenyl](methyl)amino]carbonyl}-2,2-dimethylpropylcarbamate

HRID 1865728Notes

Reaction equation

HRID 1865728 reaction equation
FC(F)(F)C(O)=O.[CH3:8][CH:9]([CH3:17])[C@H:10]([NH:15][CH3:16])/[CH:11]=[CH:12]/[C:13]#[N:14].[C:18]([O:22][C:23]([NH:25][CH:26]([C:30]([CH3:33])([CH3:32])[CH3:31])[C:27]([OH:29])=O)=[O:24])([CH3:21])([CH3:20])[CH3:19].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>ClCCl.CCCCCC.CCOCC>[C:13](/[CH:12]=[CH:11]/[C@@H:10]([N:15]([CH3:16])[C:27]([C@@H:26]([NH:25][C:23](=[O:24])[O:22][C:18]([CH3:19])([CH3:20])[CH3:21])[C:30]([CH3:33])([CH3:32])[CH3:31])=[O:29])[CH:9]([CH3:17])[CH3:8])#[N:14]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 50468592-{[(Tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acidHCID 86596608(E,4S)-5-methyl-4-(methylamino)-2-hexenenitrile trifluoroacetic acid

Product 1

HCID 86596607tert-butyl (1S)-1-{[[(1S,2E)-3-cyano-1-isopropyl-2-propenyl](methyl)amino]carbonyl}-2,2-dimethylpropylcarbamateYield 33.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21584099Diethylether hexaneSolvent

Procedure

To a solution of (E,4S)-5-methyl-4-(methylamino)-2-hexenenitrile trifluoroacetic acid (˜1.68 mmol, from Reference Example 14), 2-tert-Butoxycarbonylamino-3,3-dimethyl-butyric acid (389 mg, 1.68 mmol), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP, 916 mg, 1.76 mmol) in dichloromethane (5 mL) at 0° C. is added Hunig's base (0.877 mL, 5.04 mmol). After 5 min the cooling bath is removed. After 24 h 5% aqueous citric acid is added. The aqueous phase is washed with dichloromethane three times. The combined organic extracts are dried over anhydrous magnesium sulfate and concentrated in vacuo to give an oil. Chromatography (silica gel, hexane/ether) gave the title compound as a yellow foam (200 mg). MS (ES): m/z 352.0 (M+H)

Workup

  1. customAfter 5 min the cooling bath is removed
  2. additionAfter 24 h 5% aqueous citric acid is added
  3. washThe aqueous phase is washed with dichloromethane three times
  4. dry with materialThe combined organic extracts are dried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give an oil

Sources & evidence

ORD record
ord-8f54332b6d7241e9bcb8b63aa6f1356e
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

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